Peeples played in the Negro Leagues with the Memphis Red Sox, Kansas City Monarchs, and Indianapolis Clowns before signing with the Brooklyn Dodgers organization in 1951. He played a few years in their system at the low minors and in 1953, he bounced around among three different teams, as the Dodgers sold him to independent Keokuk before the Braves bought his contract and sent him to Evansville to finish out the season. He finished the 1953 season with a .331 average and 15 home runs. His combination of speed, average, and power were enough for the Braves to offer him a contract with the Class-AA Atlanta Crackers for the 1954 season.

The 28-year-old outfielder was hesitant when he received the news that he was going to be the one to break the league’s color barrier.

“I was sick about it because back in 1954, I didn't know how it all was going to work out. I played through the South when I was with the Kansas City Monarchs. I knew what those towns were like. Earl Mann said, ‘Well, come to spring training, and we'll see what happens.’ And that's what I did,” said Peeples in Bruce Adelson’s, "Brushing Back Jim Crow."

After the first six games of spring training, Peeples was batting an impressive .429 with a home run. His early performance caught the attention of the media, with the Sarasota Herald-Tribune running the headline on March 22, 1954, “Nat Peeples May Be 1st to Break SA Race Barrier.” The once reluctant outfielder warmed up to his prospects after his hot start.

“I think I’ve made it, but of course that’s not for me to say,” he remarked.

Peeples played well enough to make the opening day roster, but couldn’t stick with the team. He made his debut on April 9, 1954 in Mobile, Ala., grounding out in a pinch-hitting appearance. He played in one more game, finishing 0-4 with a walk, and was sent to Class-A Jacksonville on April 17, 1954. Rumors surrounding his demotion stemmed from complaints of the rest of the owners in the league. Others have asserted he simply wasn't ready for the pitching in the league.

“When Earl Mann explained on April 17 that Peeples had lost his spot on the roster to more experienced outfielders and that the Crackers had sent him to Jacksonville so he could play every day, the Atlanta owner asserted the truth. … He was an average Class-A and a below-average Class-AA player, and it took him until the end of his career to reach that level of competence. Thus, in 1954, he was clearly not ready for the Southern Association,” Fenster reported.

He stayed with the Braves organization for the majority of his career, getting as far as Triple-A before his retirement in 1960. In his 1999 interview with Adelson, Peeples took pride in his accomplishment, no matter how brief it was.

“I felt pretty good about what I did because no other black players tried to play in the Southern Association. I don’t regret what I did, but I can’t say I’d do it again. I’d have to think about it. I’d like to be remembered for what I did.”